Angiotensin receptor blocker beneficial in heart failure

Adding an angiotensin receptor blocker to existing "optimal" treatment including ACE inhibitors improves cardiovascular outcomes in patients with heart failure, a new study has shown.The CHARM study compared candesartan (target dose 32 mg once daily) and placebo in about 7,600 patients with New York Heart Association class II to IV symptoms. At baseline, 41% were receiving an ACE inhibitor, 55% a beta-blocker, 42% a lipid-lowering drug, 56% aspirin and 83% a diuretic.After a median 38 months of follow-up, the primary outcome of cardiovascular death or nonfatal myocardial infarction was reached by 20.4% of patients in the candesartan group compared to 22.9% in the placebo group (hazard ratio 0.87, p=0.004). Candesartan treatment was also associated with a significant reduction in nonfatal MI alone, and a composite of fatal MI, sudden death or nonfatal MI. Benefits were consistent across predetermined subgroups classified by criteria including age, sex, ejection fraction, diabetes status, blood pressure, and concurrent treatments.Benefits of ACE inhibitors in heart failure had been well established, initially by the SOLVD treatment and prevention trials. "Prior to CHARM, it was unknown whether angiotensin receptor blockers would also reduce MI in patients with heart failure or other cardiovascular conditions," the researchers said. The reduction in cardiovascular death and nonfatal MI from adding candesartan was similar in magnitude to the effects of ACE inhibitor treatment in SOLVD."Importantly, candesartan also further reduced risk in patients receiving an ACE inhibitor, suggesting additional protection against cardiovascular events through increased blockade of the renin-angiotensin-aldosterone (RAS) system," they said. More research was needed to confirm the findings and define the mechanisms of the benefit. While ACE inhibitors prevented bradykinin breakdown, which might be advantageous, it was possible their blockade of the RAS system was incomplete, especially during long-term treatment in patients with an activated system.Reference...